SYNTHESIS OF A CONFORMATIONALLY CONSTRAINED HEPARIN-LIKE PENTASACCHARIDE

An octasulfated pentasaccharide 1 having an L-iduronic acid moiety in a fixed C-1(4) conformation was synthesized by the coupling of a trios yl donor 3 with a disaccharide acceptor 4 followed by deprotection and O-sulfation. The acceptor 4 was prepared from the fully acetylated 5- C-allyl-beta-D-glucose building block 7 by means of a TMSOTf-promoted glycosylation, intramolecular substitution and ozonolysis of the olefi nic bond as the key reactions. Compound 1 showed very low activity in an antithrombin III-mediated anti-Xa assay; this reflects the importan ce of the presence of a flexible L-iduronic acid moiety in heparin-lik e antithrombotics.